Objective To evaluate the clinical validity and clinical utility of DNA testing in people suspected of having hereditary haemochromatosis and in family members of those diagnosed with the disorder. Design A systematic review.
Methods Fifteen electronic databases were searched up to April 2007. Studies were included for assessment of clinical validity of genotyping for the C282Y mutation for the diagnosis of hereditary haemochromatosis if they considered the use of DNA tests in Caucasians of northern European origin with iron overload suggestive of haemochromatosis compared to a control population and reported, or allowed calculation of, sensitivity and specificity. For clinical utility, studies were included if participants were Caucasians with iron overload suggestive of haemochromatosis or relatives of suspected cases, compared a diagnostic strategy incorporating DNA testing with one without DNA testing and reported patient based outcomes or some measure of cost effectiveness.
Results Eleven studies were identified that could be used to evaluate clinical validity of genotyping for the C282Y mutation for the diagnosis of hereditary haemochromatosis. Clinical sensitivity of C282Y homozygosity for hereditary haemochromatosis ranged from 28.4% to 100%; when considering studies which used strict criteria to classify hereditary haemochromatosis clinical sensitivity ranged from 91.3% to 92.4%. No clinical effectiveness studies were found. Two cost-effectiveness studies were identified which suggest that gene testing may be cost-effective.
Conclusion DNA testing for hereditary haemochromatosis in at-risk populations has clinical validity and may have clinical utility. The review highlights the limitations of the literature and methodological difficulties associated with evaluating this genetic test.